TY - JOUR
T1 - The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health
AU - Wong, B. S.
AU - Rao, A. S.
AU - Camilleri, M.
AU - Manabe, N.
AU - McKinzie, S.
AU - Busciglio, I.
AU - Burton, D. D.
AU - Ryks, M.
AU - Zinsmeister, A. R.
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Background The short-term effects of methylnaltrexone (MNTX), a peripherally acting μ-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. Aim To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. Methods In a randomized, parallel-group, double-blind, placebo-controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. Results Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t 1/2 (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). Conclusion Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health.
AB - Background The short-term effects of methylnaltrexone (MNTX), a peripherally acting μ-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. Aim To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. Methods In a randomized, parallel-group, double-blind, placebo-controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. Results Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t 1/2 (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). Conclusion Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health.
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U2 - 10.1111/j.1365-2036.2010.04422.x
DO - 10.1111/j.1365-2036.2010.04422.x
M3 - Article
C2 - 20839388
AN - SCOPUS:77956408794
SN - 0269-2813
VL - 32
SP - 884
EP - 893
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 7
ER -